FACTORS ASSOCIATED WITH DELAYED DIAGNOSIS IN PATIENTS WITH PRIMARY VITREORETINAL LYMPHOMA.

PURPOSE: To identify demographic and clinical factors associated with delayed diagnosis in patients with primary vitreoretinal lymphoma (VRL). METHODS: Retrospective, tertiary referral center-based cohort study of all patients at Mayo Clinic in Rochester, Minnesota, with a biopsy-proven diagnosis of VRL from January 1, 2000, to October 31, 2022. RESULTS: There were 87 patients included during the 22-year study period with 73 patients (83.9%) diagnosed with VRL upon initial evaluation at the tertiary center, with the other 14 patients (16.1%) diagnosed later. The median referral time was 4.8 months (range: 0-113 months). Patients who received an initial diagnosis of inflammatory uveitis or another incorrect diagnosis elsewhere were referred slower than those initially diagnosed with VRL (P = 0.04). The most common incorrect initial diagnosis from an outside institution was inflammatory uveitis (n = 35, 40.2%). When patients were split into four groups based on referral time, prior use of corticosteroids was associated with a significant delay in referral (P = 0.03). CONCLUSION: Diagnosing VRL continues to be challenging, as months-long delays from initial evaluation to expert referral center evaluation are common. Prior use of corticosteroids was associated with delay in diagnosis and referral time, underscoring the need to increase awareness regarding differences between VRL and uveitis.

INTEREST OF REGULAR ASSAYS OF AQUEOUS HUMOR INTERLEUKIN-10 LEVELS IN MONITORING OF VITREORETINAL LYMPHOMA.

PURPOSE: To investigate the variation of interleukin-10 (IL-10) levels in the aqueous humor (AH) of patients with vitreoretinal lymphoma (VRL) throughout therapy and follow-up and analyze the relation of these variations with VRL clinical course and relapse. METHODS: This study retrospectively included consecutive patients diagnosed with VRL in a single center. AH IL-10 samples and patient clinical course were evaluated. The response to treatment was evaluated according to the criteria set by the International Primary Central Nervous System Lymphoma Collaborative Group. RESULTS: A total of 59 eyes of 34 patients were included. Interleukin-10 levels decreased significantly at first AH sample after therapy induction (median [IQR] 3.0 [2.8-3.6] months) among patients in complete clinical remission (P < 0.001). Among patients in complete clinical remission with residual detectable IL-10 in AH after therapy induction (85.3% systemic chemotherapy, 11.8% intravitreal methotrexate, 2.9% palliative care), 87.5% experienced ocular relapse within 5 years. The detection of IL-10 in AH at the first visit after induction for complete clinical remission obtained a sensitivity of 77.8% (95% CI 0.45-0.96) and a specificity of 96.4% (95% CI 0.82-0.99) to predict ocular relapse. For relapsing eyes (N = 26), IL-10 significantly increased between the last IL-10 measurement and the time of the first ocular relapse (P < 0.001). In 76.0% of cases, an increase in IL-10 was detected earlier than clinical relapse with a mean (SD) of 4.0 (2.4) months. CONCLUSION: The present study suggested the usefulness of IL-10 in the prognosis of VRL. This study showed a relation between IL-10 in AH and tumoral activity, and for the first time with disease relapse.

Diagnosis and management of vitreoretinal lymphoma: present and future treatment perspectives.

Intraocular lymphoma (IOL) is a rare malignant intraocular lymphocytic tumor that mimics uveitis. IOL is anatomically classified into vitreoretinal lymphoma (VRL) and uveal lymphoma; most IOLs are VRLs, while uveal lymphoma is rare. VRL is highly malignant, with 60%-85% of patients developing central nervous system (CNS) lymphoma; primary VRL (PVRL) is an ocular disease with poor prognosis. We aimed to review the management and both current and future treatments for VRL. VRL diagnosis is based on the results of cytopathological examination using vitreous biopsy. However, the positive ratio of vitreous cytology remains 29%-70%. A combination of adjunctive tests may improve diagnostic accuracy, but as yet no gold-standard regimen has been established. Methotrexate intravitreal injections are effective in controlling ocular lesions; however, this treatment allows CNS dissemination. The efficacy of systemic chemotherapy in suppressing CNS dissemination has been recently debated. A multicenter prospective study with a unified treatment protocol is required to clarify this issue. In addition, establishing a treatment protocol for elderly patients and those with poor general health is necessary. Moreover, relapsed/refractory VRL and secondary VRL are more difficult to treat than PVRL because they are prone to recurrence. Ibrutinib, lenalidomide with or without rituximab, and temozolomide are promising treatments for relapsed/refractory VRL. In Japan, Bruton's tyrosine kinase (BTK) inhibitors have been approved for treating refractory CNS lymphoma. Furthermore, a randomized prospective study of tirabrutinib, a highly selective BTK inhibitor, is ongoing for evaluating the suppressing of CNS progression in patients with PVRL.

Diagnosis, treatment, and prognosis of primary intraocular lymphoma: Single-center real-world clinical experience.

BACKGROUND: The diagnosis and management of primary intraocular lymphoma (PIOL) remain challenging. This study identified factors indicative of PIOL, described treatment outcomes, and determined modalities to prevent relapse. METHODS: We included 21 PIOL-diagnosed patients, seven via cytology, 12 via genetic evaluation, and two via interleukin (IL) level measurements, who underwent vitrectomy and received local intravitreal methotrexate (IV-MTX) injection. Clinical outcomes, including treatment response and relapse, were compared between patients receiving IV-MTX alone (n = 13) or IV-MTX with systemic high-dose methotrexate (HD-MTX) as prophylaxis (n = 8). RESULTS: Twelve ophthalmologic and eight central nervous system (CNS) relapse cases within a median of 20.3 and 11.6 months were shown, regardless of the treatment modalities, with a median progression-free survival of 21.3 (95% confidence interval, 9.5-36.7) months. There was no difference in demographic characteristics between the two groups, except with the poorer performance status in patients in the HD-MTX prophylaxis group. Furthermore, patients demonstrated rapid elevations in the vitreous fluid IL-10/IL-6 cytokine ratio before ophthalmologic and CNS relapse. Therefore, diagnosis should be based on clinical signs and assisted by vitrectomy, cytologic, molecular, and cytokine studies. CONCLUSION: For PIOL, aggressive systemic treatment equivalent to that of primary CNS lymphoma (PCNSL) is recommended because solely HD-MTX did not prevent or delay CNS relapse. To prevent PIOL relapse in the CNS efficiently, prospective trials with large numbers of patients and advanced therapeutic regimens are necessary. Furthermore, regular clinical follow-up is crucial, and the IL-10/IL-6 ratio can help evaluate relapse promptly.

Intraocular Metastasis of Large T-cell Lymphoma Transformed from Mycosis Fungoides.

PURPOSE: To describe a rare case of intraocular lymphoma that metastasized from cutaneous mycosis fungoides and transformed to large cell T cell lymphoma resulting in vitreoretinal pathology. METHODS: Retrospective case report. RESULTS: A 57-year-old male presented with 3 months of blurred vision in the right eye. He reported only a medical history of psoriasis. Examination revealed keratic precipitates and dense vitritis in the right eye. He was taken for a diagnostic vitrectomy. Histopathology showed that atypical lymphoid cells and flow cytometry were consistent with transformed large cell T-cell lymphoma. During follow-up, pre- and inner retinal lesions were noted throughout the posterior pole. Histopathology of the psoriatic lesions was consistent with mycosis fungoides. He was initiated on systemic and intravitreal methotrexate with improvement in vision. CONCLUSIONS: Ocular involvement in metastatic transformed T-cell lymphoma is extremely rare but can be present with vitritis and retinal deposits. Our patient responded well to intravitreal methotrexate therapy.

Unusual presentation of cornea verticillata with intravitreal methotrexate in a case of primary intraocular lymphoma.

A 56-year-old woman presented with floaters and diminution of vision in the right eye for 1 week. On examination, visual acuity was 20/400 in the right eye and 20/60 in the left eye. Indirect ophthalmoscopy revealed vitritis in the right eye and subretinal deposits in both eyes. Vitreous biopsy of the right eye revealed large B-cell-type primary intraocular lymphoma and the patient underwent multiple intravitreal methotrexate injections (400 µg/0.1 mL) in the right eye and systemic chemotherapy for bilateral disease. Following biweekly injections of methotrexate, her visual acuity improved considerably from 20/400 to 20/60 with resolution of vitritis. However, following eighth dose of intravitreal methotrexate, she experienced visual decline to 20/120 along with photophobia, redness and watering. Whorl-shaped opacities, limbitis and corneal haze were noted on slit-lamp examination. Intravitreal methotrexate was stopped, and the patient was started on frequent topical lubricants, loteprednol, topical folinic acid and oral folic acid. Complete resolution of corneal toxicity was observed at 3 weeks and the injections were suspended as there was no recurrence at 6 months follow-up.

Outcomes of intravitreal methotrexate to salvage eyes with relapsed primary intraocular lymphoma.

PURPOSE: To report the outcomes of intravitreal methotrexate (MTX) injections to rescue eyes with relapsed primary intraocular lymphoma (PIOL). METHODS: Retrospective case series of patients with ocular relapse of PIOL who had initially received systemic chemotherapy (all five cases) and external beam radiotherapy (EBRT) to brain and orbits (two cases). Injections of MTX (400 µg/0.1 mL) were given one time per week for 1 month, every other week for 4 months, followed by a maintenance phase of one injection one time per month for 8 months (total of 20 injections in a year). RESULTS: From April 2008 to February 2016, there were nine eyes of five patients (three men; average age at first presentation 62 years) treated with our rescue protocol of intravitreal MTX injections. Ocular relapse occurred at a mean interval of 15 months (range 5-34 months) after the completion of initial systemic treatment. At mean follow-up of 31 months (range 5-104 months), tumour control was achieved in eight out of nine eyes (89%); one eye failed, with persistent retinal infiltrates despite increasing the frequency of injections, resulting in severe keratopathy. The only other complication occurred in one eye, developing cystoid macular oedema from MTX injections that resolved with topical anti-inflammatory medications and reduced frequency of MTX. There were no cases of reduced vision or ocular relapse, but two patients died (one of central nervous system lymphoma). CONCLUSIONS: Intravitreal MTX was a safe and effective treatment modality for relapsed PIOL after systemic chemotherapy and radiotherapy, achieving local tumour control in 89%, and hence represents an optimal choice. However, given the rare nature of PIOL, larger collaborative studies with longer follow-up are needed to corroborate this.

Clinical outcomes of intravitreal methotrexate injection protocol with a reduced initial frequency for intraocular lymphoma.

BACKGROUND/PURPOSE: To investigate the clinical characteristics of intraocular lymphoma and to evaluate two protocols of intravitreal methotrexate injection. METHODS: A retrospective chart review was conducted of newly-diagnosed intraocular lymphoma patients between January 2013 and January 2018 at National Taiwan University Hospital. Patients were divided into two groups. In Group A, intravitreal methotrexate was administered weekly for the initial 8 weeks, every 2 weeks for the following 12 weeks, and then monthly for 7 months. In Group B, intravitreal methotrexate was administered twice a week for the initial 2 weeks, weekly for the subsequent 2 weeks, once every 2 weeks for the next 1 month, and monthly for the last 10 months. RESULTS: A total of 12 patients were analyzed in the study; seven of these patients were allocated to Group A. Differences in the overall survival and progression-free survival between the two groups did not yield statistical significance. The median visual acuity was improved from LogMAR 0.46 to LogMAR 0.30 with borderline significance in Group A (p = 0.053). Two of seven patients in Group A and five of five patients in Group B developed punctate keratitis during intravitreal methotrexate injection treatment. CONCLUSION: Intravitreal methotrexate is an effective and repeatable treatment for intraocular lymphoma. A new protocol with reduced frequency of intravitreal injections as shown in this study could potentially produce similar results without a worse prognosis, along with a decrease in the incidence of keratitis.

CLINICAL FEATURES, DIAGNOSTIC SIGNIFICANCE, AND PROGNOSIS OF VITREORETINAL LYMPHOMA IN YOUNG PATIENTS.

PURPOSE: To investigate the clinical features, diagnostic approaches, and outcomes of young patients with vitreoretinal lymphoma. METHODS: Fifty-one vitreoretinal lymphoma patients (97 eyes) referred to the Eye and ENT Hospital of the Fudan University from 2011 to 2020 were grouped based on their onset age (age ≤50 years and age >50 years). Complete eye examinations, evaluation of systemic conditions, and biological analysis of intraocular fluids were performed. RESULTS: Young patients accounted for 31.4% (n = 16) of the cohort. More eyes had retinal/subretinal pigment epithelial infiltration (20 [64.5%] vs. 23 [34.8%]; P = 0.018) in young patients than in elderly ones. The mutation rate of Myeloid Differentiation Factor 88 gene (MYD88) was significantly lower in young patients than in elderly ones (5 [50%] vs. 21 [91.3%]; P = 0.016). The median time to new onset of central nervous system lymphoma was significantly shorter in young patients (11.7 vs. 36.2 months; P = 0.012). However, mean overall survival did not differ between the 2 groups (64.9 vs. 57.5 months; P = 0.871). CONCLUSION: Early diagnosis and central nervous system evaluation are crucial for young vitreoretinal lymphoma patients with rapid central nervous system involvement. Meanwhile, young vitreoretinal lymphoma patients have some unique features, including more retinal/subretinal pigment epithelial infiltrations and lower MYD88 mutation rates.

Multimodal imaging characteristics in eyes with vitreoretinal lymphoma treated with intravitreal rituximab.

PURPOSE: To characterize the imaging features in eyes with vitreoretinal lymphoma (VRL) using ultra-widefield fundus photography (UWF-FP), swept-source optical coherence tomography (SSOCT) and fundus autofluorescence (FAF) that are correlated to ongoing treatment with intravitreal Rituximab(IVR). METHODS: Retrospective observational imaging-based study of 15 treatment-naive eyes with VRL treated with IVR. All patients with primary VRL underwent vitreous biopsy using 23/25G microincision vitrectomy system for confirmation of diagnosis. All eyes received monthly IVR (1 mg/0.1 mL) injections till disease remission. Baseline clinical characteristics, treatment details, outcomes, and sequential imaging features on UWF-FP, FAF, and SSOCT were analyzed. OUTCOME MEASURES: Baseline features and changes in UWF-FP, FAF patterns, and SSOCT features in response to treatment RESULTS: Clinically, patients presented with sub-RPE deposits (n = 15), superficial retinal hemorrhages (n = 2), 'giant' RPE (retinal pigment epithelium) holes (n = 2), and anterior segment reaction (n = 1). Eyes were treated with mean 5.7 IVR injections (median: 5; range 1-13) over a mean 7.2 ± 4.9 months. During the course of treatment, two eyes developed superficial retinal hemorrhages with spontaneous resolution, 2 eyes developed CME, and 4 eyes developed characteristic 'leopard skin' pigmentation. Hyper-autofluorescence corresponding to areas of active lesions decreased with each treatment cycle and was finally replaced by hypo-autofluorescence. Serial OCTs showed regression of sub-RPE/subretinal deposits (n = 15), ellipsoid zone disruption (n = 9), and its resolution with treatment (n = 3), epiretinal membrane (ERM; n = 6), choroidal hyperreflective foci (HRF; n = 4), disorganization of retinal inner layers (DRIL; n = 3), RPE-rip (n = 2), cystoid macular edema (CME; n = 2), and hyperreflective lesions in the choroid (n = 1). Complete resolution was observed in all eyes with extensive hypo-AF. The central foveal thickness decreased from 237 ± 113 µ to 182 ± 114 µ (p = 0.1) and subfoveal choroidal thickness decreased from 258 ± 66 µ to 220 ± 64 µ (p = 0.12) at final follow-up. The mean baseline BCVA was logMAR 0.9 ± 0.9 that deteriorated to mean logMAR 1 ± 1 final visit (p = 0.7). The mean recurrence-free follow-up was 5.9 ± 5.1 months CONCLUSION: Multimodal imaging provides novel insights into features of VRL, a better understanding of regression patterns, and prognostication of outcomes when treated with intravitreal rituximab. Larger, multicentric studies with longer follow-up will help unravel imaging biomarkers to understand these aspects better.

Intravenous high-dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: An LOC network study.

The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011 and 2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 42/59 (71%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.

Efficacy and safety of intravitreal methotrexate for vitreo-retinal lymphoma - 20 years of experience.

Vitreo-retinal lymphoma (VRL) is the most common intraocular lymphoma and is highly associated with central nervous system (CNS) lymphoma (CNSL), both posing a therapeutic challenge. We investigated patients' characteristics, efficacy and safety of intravitreal methotrexate (MTX) injections and their outcomes over 20 years. The records of 129 patients diagnosed between 1997 and 2018 were retrospectively reviewed. Lymphoma involved both the CNS and vitreo-retina (49%), solely the CNS (37%) or solely the vitreo-retina (14%). In all, 45·5% of the patients with CNSL either presented with VRL or developed it after a mean (±SE) of 85·7 (7·3) months. In all, 66·0% of the patients diagnosed with VRL either presented with CNSL or developed it after a mean (±SE) 42·6 (7·6) months. The 81 patients with VRL (134 eyes) received a mean (±SD) of 19 (7) injections; however, only 5 (4) injections were needed to reach complete remission. Local recurrence occurred in two of the 81 patients. Overall, 80·2% of eyes had an initial moderate-severe visual loss, and >50% of them improved. Reversible keratopathy was the most prevalent side-effect. A total of 18·5% developed intraocular pressure (IOP) elevation due to angle neovascularisation after 16 injections, which could be reversed with prompt intravitreal injection of bevacizumab. Intravitreal MTX injections are a safe and effective treatment for VRL. Fewer injections (15) may offer similar results with fewer side-effects.

Intravitreal rituximab monotherapy for management of eyes with vitreoretinal lymphoma: initial experience from India.

PURPOSE: To evaluate treatment outcomes and complications of intravitreal rituximab (IVR) monotherapy for eyes with vitreoretinal lymphoma (VRL). METHODS: Patients diagnosed with 'isolated primary VRL' or 'VRL with remission of systemic disease' and treated with IVR (1 mg/0.1 ml) between June 2014 and June 2019 were included in this retrospective, interventional case series. Injections were repeated at monthly intervals until complete resolution. All patients signed a written informed consent form. Institutional review board approval was obtained. RESULTS: Twelve eyes of 7 patients with VRL were treated with 77 IVR injections at mean 6.42 injections per eye (median = 5; range = 2-13) for complete resolution at mean 8.16 ± 4.62 months (median = 6.97 months; range = 1.97-14.33 months). Mean age at presentation was 53.3 years (median = 54 years; range = 34-74 years). Patients were co-managed with medical oncologist and periodically evaluated. Complications included anterior uveitis (n = 6), raised intraocular pressure (n = 3), posterior synechiae (n = 2), vitreous haemorrhage (n = 1), pre-retinal haemorrhage (n = 1), retinal detachment (n = 1), posterior subcapsular cataract (n = 2) and sectoral iris atrophy (n = 1). Recurrences were seen in 3 eyes (25%), which eventually achieved complete resolution with treatment. None of the patients had systemic involvement or death during follow-up. Mean follow-up was 18.73 ± 8.83 months (median = 21.60 months; range = 7.37-32.67 months). CONCLUSION: Intravitreal rituximab monotherapy is effective in management of vitreoretinal lymphoma in patients with isolated ocular disease.

Clinical Experience in a Large Cohort of Patients with Vitreoretinal Lymphoma in a Single Center.

Background/aims: To report our five-year experience on vitreoretinal lymphoma (VRL) as a single-center tertiary hospital. Methods: The ophthalmic, cytopathology, and onco-hematologic records of patients with VRL consecutively seen from 2014 to 2019 were reviewed. Results: Fifty-nine eyes of 31 patients with large B-cell VRL were included. Eighty-one percent has developed central nervous system lymphoma at the end of follow-up. Several different imaging findings were noted, including vitritis, leopard spot appearance, Bruch's membrane/RPE infiltrations, and ellipsoid zone disruption. A variable combination of MYD88-L265P mutation in the aqueous and/or in the vitreous and positive cytology/histology allowed to reach a definite diagnosis in all the patients. Therapies included intravitreal injections of methotrexate and rituximab, systemic chemotherapy, pan-encephalic radiotherapy, and hematopoietic stem cell transplantation. Conclusion: No definite guidelines exist for VRL management. It is crucial to collect as much data as possible from tertiary referral hospitals, which suitably manage a conspicuous number of VRL patients.

Optic Nerve Infiltration in Systemic Metastatic Retinal Lymphoma (SMRL): Multimodal Imaging and Challenges in Diagnosis.

A 45-year-old man was diagnosed with diffuse large B-cell lymphoma stage IV which was confirmed by celiac lymph node biopsy. He subsequently completed six cycles of R-CHOP chemotherapy. Six months later, he presented with panuveitis OU with positive relative afferent pupillary defect OD. OCT revealed hyper-reflective lesions and irregularity of the retinal pigment epithelium OU. Fundus fluorescein angiogram shows hyper-auto fluorescence and granular changes on the retina. A month later, he developed swollen optic disc OD and hemorrhagic retinitis OU and treated as presumed CMV retinitis. Anti-TB was started after a positive Mantoux test. He finally consented for a vitreous biopsy which showed atypical lymphoid cells highly suggestive for vitreoretinal lymphoma and subsequently received intravitreal methotrexate OU.Conclusion: Optic nerve infiltration in systemic metastatic retinal lymphoma may have initial occult signs but with profound visual loss. Ocular infections like CMV retinitis and tuberculosis may mask and delay the diagnosis in immunocompromised patients.

Primary Vitreoretinal Lymphoma in HIV Infection.

Purpose: To describe the epidemiology, clinical characteristics, diagnosis and treatment of human immunodeficiency virus (HIV)-related primary vitreoretinal lymphoma (PVRL).Methods: Narrative literature review.Results: HIV-related PVRL occurs in persons who are relatively young and generally have very low CD4+ T-cell counts. Vitritis with subretinal or sub-retinal pigment epithelial infiltrates is typical. Vitreous cytology remains the gold standard for diagnosis, supplemented by flow cytometry and genetic analyses of tumor cells, and measurement of aqueous or vitreous interleukin-10 levels. Concurrent brain involvement also may establish the diagnosis. Treatment includes antiretroviral therapy (ART), systemic chemotherapy (usually methotrexate-based) and local ocular treatment (intravitreal methotrexate, intravitreal rituximab, external beam radiotherapy). Systemic chemotherapy is of uncertain value for PVRL without other central nervous system involvement. Prognosis is poor, but has improved significantly compared to the pre-ART era.Conclusions: Ophthalmologists should consider the diagnosis of PVRL in HIV-positive individuals who present with intermediate or posterior uveitis.

Multidisciplinary Diagnostic Approach in Intraocular Lymphoma Featuring Pseudo-hypopyon: Case Series and Literature Review.

PURPOSE: Diagnosis of intraocular lymphoma (IOL) is usually achieved by histopathological analysis. However, it may lead to inconclusive results due to the scarcity of malignant cells obtained by biopsy, hence leading to delayed diagnosis. We report two cases of IOL with pseudo-hypopyon, a rare feature of IOL, as their initial ocular feature, diagnosed using a multidisciplinary diagnostic approach. Common clinical features of IOL with pseudo-hypopyon were also investigated. METHODS: Retrospective case series and literature review. RESULTS: Two cases of IOL, a 78-year-old female and a 59-year-old male, whom had been diagnosed with systemic B-cell lymphoma developed pseudo-hypopyon and visual impairment during the course of their chemotherapy. Diagnosis of IOL was achieved from anterior chamber aspiration samples with supplementary diagnostic tools including flow cytometric immunophenotyping, interleukin and IgH gene rearrangement analysis in addition to the conventional histopathological analysis. Generally, pseudo-hypopyon was more commonly seen in secondary IOL and may associate with hyphema and high intraocular pressure. CONCLUSION: Pseudo-hypopyon is a rare feature of IOL, more commonly seen in secondary IOL, which can be accompanied by hyphema and high intraocular pressure. Supplementary diagnostic tools such as flow cytometric immunophenotyping, interleukin analysis, and immunogloblin H gene rearrangement analysis are useful for supporting the diagnosis of IOL with pseudo-hypopyon.

Serial Detection of MYD88 L265P Mutation in the Aqueous Humor of a Patient with Vitreoretinal Lymphoma for Disease Monitoring.

PURPOSE: To report a case of a patient whose MYD88 mutation disappeared from the aqueous humor following treatment with intravitreal methotrexate. METHODS: A retrospective review of clinical, histopathological and imaging records. RESULTS: A 49-year-old woman presented with bilateral primary vitreoretinal lymphoma confirmed by molecular and next-generation sequencing studies on vitreous biopsy samples. Initially, the MYD88 L265P mutation was detected in aqueous samples of both eyes. Serial testing for MYD88 L265P mutations performed on aqueous samples collected at the time of the weekly intravitreal methotrexate injections showed the mutation ceased to be detected after four weekly injections in the non-vitrectomized right eye and after two weekly injections in the vitrectomized left eye. Clinical improvement accompanied the negativization of the mutation in both eyes. CONCLUSION: We present a case that demonstrates the possible utilization of serial testing for the MYD88 L265P mutation as a tool for monitoring disease course in vitreoretinal lymphoma.

Serial changes in the aqueous IL-10 level after intravitreal methotrexate injection as an indicator of primary vitreoretinal lymphoma recurrence.

Primary vitreoretinal lymphoma (PVRL) often masquerades as other uveitic diseases. We investigated the aqueous cytokine level changes and the effects of intraocular methotrexate (MTX) in patients with PVRL. In this retrospective consecutive case-series study, we reviewed the records of 14 consecutive patients with PVRL treated between 2018 and 2020. The concentrations of interleukin (IL)-2, IL-6, IL-10, IL-12, IL-17, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were determined at baseline and several time points after intravitreal MTX injections during follow-up. Markedly elevated IL-10 levels and a higher IL-10/IL-6 ratio were found in patients with PVRL. The aqueous levels of IL-10, IL-12, and TNF-α, and the IL-10/IL-6 ratio significantly decreased at 1 month after intravitreal MTX therapy onset compared with the baseline values (P = 0.001, 0.002, 0.001, and 0.001, respectively). The mean duration to normalized IL-10 levels was 1.17 ± 0.4 months. Where serially recorded IL-10 levels were available, regular intravitreal MTX treatment was associated with rapid reduction in IL-10 levels, while elevated IL-10 level was associated with disease recurrence. Elevated IL-10 levels and high IL-10/IL-6 ratio may aid in the diagnosis of PVRL. Aqueous IL-10 level monitoring can help assess the therapeutic response and indicate disease recurrence.